At birth and for the first two postnatal weeks, the small intestine of the rat is relatively immature. During the third and fourth weeks it undergoes an array of changes and by the end of this period, exhibits the same digestive and absorptive characteristics as in the adult. The spontaneous process of weaning occurs concurrently with these intestinal changes. The broad aim of this project is to establish how the timing and nature of the developmental changes of the intestine are regulated. The enzyme sucrase is a convenient marker, for its activity is absent from the intestine until postnatal day 16, after which it increases rapidly, reaching adult levels by day 25. We have shown that the timing of appearance of sucrase is primarily controlled by plasma corticosterone, but soon after appearing the enzyme loses glucocorticoid-responsiveness and by day 25 is under dietary regulation instead. We are now proposing to determine: 1) the molecular basis for glucocorticoid independence, 2) the biochemical details of the dietary phase of control, and 3) whether other enzymes show the same loss of glucocorticoid-responsiveness and acquisition of dietary dependence. We will also investigate the possibility that the intestine becomes increasingly responsive to corticosterone during the first two postnatal weeks due to facilitation of one or more steps involved in the action of this hormone. One of the most striking features of the neonatal intestine is its efficient absorption of metals including those of nutritional importance (e.g., iron and calcium) and the toxic heavy metals (e.g., lead and cadmium). During the third and fourth postnatal weeks, there is a sudden decline in the capacity for metal absorption. We will determine whether: 1) this reflects a non-selective transport mechanism for metals during the neonatal period, and 2) the developmental decline of metal absorption is causally related to either plasma corticosterone or the dietary transition of weaning.